Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes

Last updated: June 4, 2024
Sponsor: University of Washington
Overall Status: Active - Recruiting

Phase

4

Condition

Diabetes Prevention

Diabetes Mellitus, Type 2

Diabetes And Hypertension

Treatment

Placebo

Semaglutide Auto-Injector

Clinical Study ID

NCT05780905
STUDY00016594
U1111-1271-3352
  • Ages 40-65
  • All Genders

Study Summary

A human subjects research study, the primary purpose of which is to assess the EFFECTS OF SEMAGLUTIDE ON INTRACRANIAL BLOOD FLOW AND BLOOD-BRAIN BARRIER PERMEABILITY IN TYPE-2 DIABETES (T2D) through testing of the intervention on patients in a clinical setting. The study will randomize subjects with diabetes to either semaglutide or matching placebo. Magnetic resonance images will be primary endpoint measured at baseline and at one year to assess effect of this FDA approved medication.

Given the available evidence supporting the neuroprotective effect of this drug class and stroke reduction with semaglutide, and the investigators preliminary data showing that T2D had significantly reduced total number of distal arterial branches in the brain than non-T2D, the investigators expect treatment with semaglutide will be associated with improved intracranial blood flow condition.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Men and women 40-65 years of age

  2. Subjects with type-2 diabetes >= 3 years and HbA1C 7%-10% with blood sugar controlmedications including insulin, metformin, sulfonylureas, or SGLT2 inhibitors

  3. Medically stable

  4. Has not received any investigational drug in the past 6 months

  5. Willing to participate and sign informed consent.

Exclusion

Exclusion Criteria:

  1. Contraindication to MRI or contrast agent

  2. eGFR<45 mL/min/1.73m2 (eGFR is a measurement of kidney function)

  3. Currently treated with glucagon-like peptide-1 receptor antagonist (same drug classas study intervention)

  4. Unable to perform home-glucose monitoring

  5. Currently need more than 100 units of insulin daily

  6. Uncontrolled hypertension with systolic blood pressure (SBP)>180 mmHg or diastolicblood pressure (DBP)>100 mmHg

  7. LDL-C>130 mg/dL or not on stable statin therapy in the past 6 months

  8. Treatment with pioglitazone in the past 3 months

  9. History of pancreatitis

  10. History of myocardial infarction, stroke or transient ischemic attack

  11. History or family history of Medullary Thyroid Carcinoma (MTC) or Multiple EndocrineNeoplasia syndrome type 2 (MEN 2)

  12. Hypersensitivity to semaglutide or any of the product components

  13. Participating in other clinical trial

  14. Women of child-bearing potential (ie, those who are not chemically or surgicallysterilized or who are not post-menopausal) who have a positive pregnancy test atenrollment or who are breastfeeding or who plan to become pregnant in the next 15months.

Study Design

Total Participants: 50
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 4
Study Start date:
January 11, 2024
Estimated Completion Date:
December 31, 2026

Study Description

The investigators preliminary data showed that T2D had significantly reduced total number of distal branches as assessed using the investigators quantitative magnetic resonance angiography (MRA) feature measurement method (iCafe) than non-T2D. This reduction represents a decrease in intracranial blood flow condition and can be an indication for ischemia. Clinical trial showed that semaglutide reduces stroke incidence in T2D. The investigators are conducting a randomized, double blind and placebo-controlled study to investigate the biological basis of the observed stroke reduction with semaglutide by demonstrating semaglutide can improve intracranial blood flow condition and reduce bloodbrain barrier (BBB) permeability. The investigators working hypothesis is that it is known that semaglutide has beneficial effects on T2D, therefore, it improves endothelial function for a better cerebral flow condition. However, semaglutide may also improve cerebral flow independently from glucose lowering. Together, the improved cerebral flow condition results in stroke reduction. In order to investigate the independent effects of semaglutide on intracranial blood flow condition and BBB permeability, the investigators will have a designated diabetes care specialist unblinded to the study randomization to carry out glucose management to achieve HbA1C<7.5% for both treatment groups.

Connect with a study center

  • University of Washington - Harborview Medical Center

    Seattle, Washington 98104
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.